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This work was supported by Pro-Reitoria ? de Pesquisa da UFPA (PROPESP, UFPA, Brazil), Brazilian National Council for Scientific and Technological Development (CNPq, Grant n. 435093/2018-5) and Coordena?ao ? de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)- Finance Code 001. Federal University of Par?. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. University of S?o Paulo. Bauru Dental School. Department of Biological Sciences. Bauru, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura Celular e Citogen?tica. Ananindeua, PA, Brasil. University of S?o Paulo. Bauru Dental School. Department of Biological Sciences. Bauru, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura Celular e Citogen?tica. Ananindeua, PA, Brasil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Molecular Pharmacology. Bel?m, PA, Brazil. Federal University of Par?. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Bel?m, PA, Brazil. Long-term exposure to high concentrations of fluoride (F) can damage mineralized and soft tissues such as bones, liver, kidney, intestine, and nervous system of adult rats. The high permeability of the blood?brain barrier and placenta to F during pregnancy and lactation may be critical to neurological development. Therefore, this study aimed to investigate the effects of F exposure during pregnancy and lactation on molecular processes and oxidative biochemistry of offspring rats? hippocampus. Pregnant Wistar rats were randomly assigned into 3 groups in accordance with the drinking water received: G1 ? deionized water (control); G2 ? 10 mg/L of F and G3 ? 50 mg/L of F. The exposure to fluoridated water began on the first day of pregnancy and lasted until the 21st day of breastfeeding (when the offspring rats were weaned). Blood plasma samples of the offspring rats were collected to determine F levels. Hippocampi samples were collected for oxidative biochemistry analyses through antioxidant capacity against peroxyl (ACAP), lipid peroxidation (LPO), and nitrite (NO2 ? ) levels. Also, brainderived neurotrophic factor (BDNF) gene expression (RT-qPCR) and proteomic profile analyses were performed. The results showed that exposure to both F concentrations during pregnancy and lactation increased the F bioavailability, triggered redox imbalance featured by a decrease of ACAP, increase of LPO and NO2 ? levels, BDNF overexpression and changes in the hippocampus proteome. These findings raise novel questions regarding potential repercussions on the hippocampus structure and functioning in the different cognitive domains.

Water fluoridation is the most widespread measure to prevent dental caries but its relationship with the development of type-1 diabetes (T1D), which has been increasing by 2–5% worldwide, is not quite well understood. Aim This study evaluated if fluoride (F) administered in the drinking water can prevent or reduce the development of T1D in non-obese diabetic (NOD) mice, as well as to explore the underlying mechanisms. Materials and methods Twenty-four weaning NOD mice received water containing 0, 10 or 50 ppm F for 21 days. Plasma glucose and insulin were analyzed. Quantitative proteomic analysis was conducted in the liver and gastrocnemius muscle. Results Animals treated with 10 ppm F had significantly lower glucose levels than the control group, but there was no significant difference among the groups in relation to insulin. The % of β-cell function was significantly higher in the 10 ppm F group. Changes in the proteomic profile of muscle and liver were seen among the groups. In the muscle, the 10 ppm F group presented, when compared with control, increased expression of proteins involved in energy metabolism. The 50 ppm F group, compared with control, presented increased expression of proteins related to muscle contraction, differentiation of brown adipose tissue and apoptosis. For the liver, the 10 ppm F group had increase in proteins involved in energy metabolism and protein synthesis, in respect to control. There was also an increase in isoforms of Glutathione S transferase, which was confirmed by Western blotting. In the group treated with 50 ppm F, proteins related to ROS metabolism and energetic metabolism were altered. Conclusion Increased expression of antioxidant proteins by treatment with low F concentration may possibly help to explain protection against the development of T1D, which should be better explored in future mechanistic studies.